Project Summary/Abstract There has been a broad movement in psychological science, stemming from the Research Domain Criteria initiative by the National Institute of Mental Health, to study the core features of mental disorders by integrating data across levels of information (?from genomics and circuits to behavior and self-report?). Given the vast heterogeneity among those with alcohol use disorders (AUD), there has been a recent call to establish a similar Alcohol and Addictions Research Domain Criteria (AARDoC). Investigators at the National Institute on Alcohol Abuse and Alcoholism have proposed the Addictions Neuroclinical Assessment (ANA) as an organizing framework for carrying out AARDoC research, with the goal of establishing a common assessment battery to be used by researchers and clinicians. The ANA consists of three core domains that are derived from disrupted neurocircuitry in addiction: negative emotionality, incentive salience, and executive dysfunction. The ANA holds promise as a more effective way to characterize individuals with AUD and may lead to better individual treatment matching based on core neurobiologically-derived phenotypes. However, additional validation of the ANA domains must be conducted. The aims of the proposed research study will fill important gaps in the literature by validating the three ANA domains in a new and diverse sample of individuals with AUD (Aim 1), examining how the ANA domains relate to drinking behavior at baseline as well as how changes in ANA domains relate to changes in drinking over a three-month time period (Aim 2), and, as an exploratory aim, evaluating sex differences in ANA domains and sex differences in the relationship between drinking and ANA domains (Aim 3). In order to achieve these aims, this study will leverage data (N=264) from two longitudinal studies with nearly identical recruitment and assessment strategies. Both studies conducted in depth assessment, including neuroimaging, neuropsychological, behavioral, and self-report measures, assessed at an initial assessment and at a three-month follow-up. Importantly, the included studies represent AUD diversity in several key ways: the individuals in these samples report a range of AUD severity, they vary with respect to treatment-seeking status including many non-treatment seekers who are representative of the majority of individuals who meet criteria for AUD, and the sample is diverse in terms of racial/ethnic and socioeconomic representation. Thus, this combined sample provides rich data from across levels of analysis (neurocircuitry, cognitive, behavioral, self-report) and presents a unique opportunity to use advanced quantitative methods, including exploratory structural equation modeling (Aims 1, 2, and 3), latent change score modeling (Aim 2), and measurement invariance testing (Aims 2 and 3), to further validate the ANA domains and explore how they relate to changes in drinking behavior over time. Findings from this study will be important for testing AARDoC and how AARDoC domains relate to clinically relevant alcohol behavior change. Ultimately, findings will inform measurement-based care and precision medicine in AUD.